Alleviating breathlessness in patients with cancer with dexamethasone (ABCD): A parallel-group, double-blind, randomized clinical trial (RCT).
Authors: David Hui, Veronica Puac, Zeena Shelal, Rony Dev, Sandra Hanneman, Kristofer Jennings, Hilary Y. Ma, Diana L. Urbauer, Sanjay Shete, Frank V. Fossella, Zhongxing X. Liao, George R. Blumenschein, Joe Y. Chang, Michael O'Reilly, Saumil Gandhi, Anne S. Tsao, Donald Mahler, Eduardo Bruera
Journal: Journal of Clinical Oncology (2022)

12112 Background: Systemic corticosteroids are commonly prescribed for palliation of dyspnea in patients with cancer; however, evidence to support their use is limited. A small RCT suggested that dexamethasone may be efficacious. In this confirmatory RCT, we compared the effect of high dose dexamethasone and placebo on dyspnea in patients with cancer. Methods: This NCI-funded, multi-site, double-blind, parallel group RCT enrolled ambulatory patients with cancer, age ≥18, dyspnea ≥4/10 and randomly assigned them to receive dexamethasone 8 mg orally every 12 hours for 7 days followed by 4 mg orally every 12 hours for 7 days or matching placebo capsules. Permuted block randomization (block size = 6, 2:1) was conducted, stratified by baseline dyspnea and study site. Patients, research staff and clinicians were blinded. The primary outcome was change in average dyspnea intensity assessed with a 0-10 numeric rating scale (0 = none, 10 = worst) between baseline and day 7. Secondary outcomes included the Edmonton Symptom Assessment Scale (ESAS) and adverse effects (CTCAE v4.02). Intention-to-treat analysis was conducted with linear models to compare between groups. The planned sample size of 201 patients provided 80% power to detect a mean difference of 1.0 between treatment groups with a two-sided α of 5%, assuming a standard deviation of 2.0 and 15% attrition. (Clinicaltrials.gov NCT03367156). Results: Between 1/11/2017 and 4/23/2021, we enrolled 149 patients and 128 received the blinded study interventions (dexamethasone n = 85, placebo n = 43). Enrollment was terminated early by the Data Safety Monitoring Board when futility criterion was met in pre-planned interim analysis. The mean change in dyspnea NRS intensity between baseline and day 7 was -1.6 (95% CI -2, -1.2) in the dexamethasone group and -1.6 (95% CI -2.3, -0.9) in the placebo group, with no significant between-group difference (mean 0, 95% CI -0.8, 0.7; P = 0.91). Secondary analyses showed that the dexamethasone group had a significantly better ESAS appetite (mean difference -1.2, 95% CI -2.2, -0.1; P = 0.03) and well being (mean -1, 95% CI -1.8, -0.2; P = 0.02), and worse ESAS anxiety (mean 1.1, 95% CI 0.3, 1.9; P = 0.01) and depression (mean 0.9, 95% CI 0.1, 1.7; P = 0.02) compared to placebo. Similar magnitude of changes in dyspnea and ESAS symptoms were observed by day 14. Adverse effects were reported more frequently in the dexamethasone group (any grade): insomnia (38% v. 12%), neuropsychiatric symptoms (31% vs. 7%), infections (21% v. 12%), dyspepsia (26% v. 12%), edema (18% v. 9%), hiccups (12% v. 7%), flushing (9% v. 5%) and respiratory distress (6% v. 0%). More patients in the dexamethasone group required hospitalization within 30 d of last study medication (25% vs. 7%, P = 0.02). Conclusions: High dose dexamethasone did not improve dyspnea in patients with cancer more than placebo and was associated with more adverse events. Clinical trial information: NCT03367156.